title: Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice.
abstract: Budesonide, a synthetic glucocorticoid used for treating asthma, and pioglitazone, a synthetic peroxisome proliferator-activated receptors γ ligand used for the treatment of diabetes, were evaluated for their combinational chemopreventive efficacy on mouse lung cancer using female A/J mice with benzo(a)pyrene used as the carcinogen. All chemopreventive treatments began 2-wk post-carcinogen treatment and continued daily for 20 wk. Budesonide was administered by the aerosol route using an improved aerosol delivery system. Pioglitazone was introduced by oral gavage. The characterization of drug distribution showed that budesonide introduced by aerosol delivery accumulated only in the lung. Budesonide alone reduced tumor load by 78% and pioglitazone alone reduced tumor load by 63%. By combining aerosolized budesonide with pioglitazone, the inhibition on tumor load was 90%. In vitro experiments using human cancer cells showed that budesonide and pioglitazone exhibited independent, additive inhibitory effects on cell growth. Our results provide evidence that aerosolized budesonide and oral pioglitazone could be a promising drug combination for lung cancer chemoprevention.
authors.affiliation: Department of Energy, Environmental and Chemical Engineering, Washington University in St Louis, St Louis, Missouri 63110, USA.
authors.forename: Huijing
authors.initials: H
authors.lastname: Fu
authors.forename: Jingjie
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Weidong
authors.initials: W
authors.lastname: Wen
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Lubet
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.forename: Ruth
authors.initials: R
authors.lastname: Chen
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Da-Ren
authors.initials: DR
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001564:Benzo(a)pyrene; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000473:pathology; D018890:Chemoprevention; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008805:Mice, Inbred A; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D002273:Carcinogens; D005938:Glucocorticoids; D045162:Thiazolidinediones; D001564:Benzo(a)pyrene; D019819:Budesonide; D000077205:Pioglitazone